GLP-1 RA Discontinuations Frequent in People with Obesity Without Diabetes

Credit: Kenny Eliason/Unsplash

Greater discontinuation of glucagon-like peptide-1 (GLP-1) receptor agonists was found among individuals with overweight and obesity without type 2 diabetes (T2D) in a time-restrained systematic review and meta-analysis of observational real-world data.¹

Pooled estimates among 11 identified studies reported approximately 49% of patients with overweight and obesity discontinuing GLP-1 RA medications before the 1-year mark, inconsistent with their intended long-term use, but aligning with adherence rates observed for other chronic disease medications.

“Our findings indicate that nearly half of patients who begin a GLP-1 receptor agonist will discontinue within a year, though substantial inter-study variability was observed. The proportion of patients with T2D explained a significant proportion of the variation between studies,” wrote the investigative team, led by Gregory J. Grosicki, PhD, department of scientific and clinical affairs at Medifast, Inc.

Obesity management has evolved simultaneously with the development of new-generation GLP-1 receptor agonists for T2D, which have shown greater reductions in body weight than previous drugs or lifestyle interventions.² Although rates remain high in the United States at nearly 40%, there has been no increase in obesity in 2023, denoting the first time in more than a decade.

Many physicians have championed the long-term use of GLP-1 agonists, but literature has pointed to high discontinuation rates, which could lead to weight regain and a reduction in cardiometabolic benefit.³ Some real-world data pointed to a 1-year discontinuation rate of up to 74%.⁴ For this systematic review, Grosicki and colleagues surveyed PubMed to identify real-world studies reporting 1-year discontinuation rates for GLP-1s.¹

The team excluded studies published before 2021 or did not examine records extending to at least 2021, citing the approval date of the new-generation GLP-1s, including semaglutide, for weight management. A random-effects meta-analysis estimated the pooled 1-year discontinuation rates of GLP-1 agonists across each included trial.

An initial search identified 628 studies, of which 323 remained after filtering for publication data. A further 214 exclusions were made for improper type, with an evaluation of full-text articles leaving 9 eligible for study inclusion. The median sample size of the included texts was 5103 patients and the 1-year discontinuation rate was 50.1%

Upon analysis, the pooled 1-year discontinuation rate from the random-effects meta-analysis was 48.7% (95% CI, 39.8–57.5). Meta-regression assessing the link between the proportion of patients with T2D and the 1-year discontinuation rate found a significant negative association (adjusted R2, 61.6%). For each 1% increase in the proportion of patients with T2D, the 1-year discontinuation rate decreased (β, –0.37; 95% CI, –0.57 to –0.17; P = .003).

Among the studies directly reporting reasons for GLP-1 discontinuation (n = 12) or assuming reasons (n = 3), 1 cited adverse gastrointestinal (GI) events, high out-of-pocket costs, medication shortages, and a perceived lack of benefit. Meanwhile, 6 studies linked prognostic factors, including younger age, lower income, and male sex, to a higher GLP-1 discontinuation rate.

“To support long-term weight loss maintenance in this growing user group, barriers to continued GLP-1 RA treatment should be addressed through testing strategies such as patient and health insurer education on the chronicity of obesity, the long-term cost-effectiveness of sustained treatment and the importance of lifelong transformation through the integration of long-term medication use and healthy habits,” Grosicki and colleagues wrote.

References

1. _{Grosicki GJ, Thomas JG, Dhurandhar NV, Lofton H, Heymsfield SB, Jonnalagadda SS. Glucagon-like peptide-1 receptor agonists discontinuation is higher in individuals with overweight and obesity without type 2 diabetes. Diabetes Obes Metab. Published online January 2, 2025. doi:10.1111/dom.16151}
2. _{Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038}
3. _{Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725}
4. _{Haase CL, Serratore Achenbach MG, Lucrezi G, Jeswani N, Maurer S, Egermann U. Use of Liraglutide 3.0 mg for Weight Management in a Real-World Setting in Switzerland. Obes Facts. 2021;14(5):568-576. doi:10.1159/000518325}